title: Allopurinol and nitric oxide activity in the cerebral circulation of those with diabetes: a randomized trial.
abstract: OBJECTIVE
  Type 2 diabetes increases risk of stroke, perhaps because of impaired cerebrovascular basal nitric oxide (NO) activity. We investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol.
  
  
  METHODS
  We performed a randomized, double-blind, placebo-controlled crossover study. We measured the response to infusion of NG-monomethyl-L-arginine (l-NMMA) in males with type 2 diabetes before and after allopurinol or placebo. The primary end point was the change in internal carotid artery flow following L-NMMA infusion, expressed as the area under the flow-per-time curve.
  
  
  RESULTS
  We enrolled 14 participants. Allopurinol improved responses to L-NMMA when compared with responses associated with placebo (P = 0.032; median reduction in internal carotid artery flow following L-NMMA of 3,144 ml [95% CI 375-7,143]).
  
  
  CONCLUSIONS
  Xanthine oxidase inhibition with allopurinol appears to improve cerebral NO bioavailability, as evidenced by a greater response to infusion of L-NMMA.
authors.affiliation: Acute Stroke Unit, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, UK. j.dawson@clinmed.gla.ac.uk
authors.forename: Jesse
authors.initials: J
authors.lastname: Dawson
authors.forename: Terry
authors.initials: T
authors.lastname: Quinn
authors.forename: Craig
authors.initials: C
authors.lastname: Harrow
authors.forename: Kennedy R
authors.initials: KR
authors.lastname: Lees
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Weir
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Cleland
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Walters
mesh_terms: D000493:Allopurinol / Q000097:blood / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D010919:Placebos; D020521:Stroke / Q000517:prevention & control; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010919:Placebos; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000493:Allopurinol